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Genes adopt non-optimal codon usage to generate cell cycle-dependent oscillations in protein levels
Milana Frenkel-Morgenstern1, Tamar Danon, Thomas Christian
1Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel. milana.frenkel@weizmann.ac.il
Molecular Systems Biology
|March 1, 2012
Summary
Cells exploit codon wobbling to regulate protein synthesis during the cell cycle. Transfer RNA (tRNA) expression oscillates, influencing gene expression and protein dynamics across cell cycle phases.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The cell cycle is a fundamental biological process controlling DNA synthesis and cell division.
- Gene expression patterns vary significantly across different phases of the cell cycle.
- Codon usage bias is known to influence translation efficiency and protein production.
Purpose of the Study:
- To investigate the relationship between codon usage bias and cell cycle regulation.
- To determine if codon preferences differ for genes expressed during specific cell cycle phases.
- To explore the role of transfer RNA (tRNA) expression in mediating cell cycle-dependent protein dynamics.
Main Methods:
- Comparative analysis of codon usage in cell cycle-regulated genes versus other genes.
- Empirical measurement of transfer RNA (tRNA) expression levels across cell cycle phases.
- Mathematical modeling to simulate the impact of codon usage on cell cycle regulation.
Main Results:
- Cell cycle-regulated genes show a significant preference for non-optimal codons compared to other genes.
- Genes encoding proteins with cyclical expression patterns also exhibit non-optimal codon preferences.
- Transfer RNA (tRNA) expression peaks in the G2 phase and is lowest in late G1, correlating with codon usage of concurrently expressed genes.
- Protein levels of specific tRNA synthetases oscillate, peaking in G2/M phase.
Conclusions:
- Non-optimal (wobbly) codon matching influences protein synthesis dynamics during the cell cycle.
- Cells utilize codon usage and tRNA availability as a mechanism for cell cycle-dependent protein regulation.
- Codon usage bias provides a novel layer of control for generating cell cycle-specific protein levels.
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